The efficient use of organic pesticides is often restricted by their inherent poor water-solubility.
Generally, these water-insoluble organic pesticides can be applied to a site or substrate in three ways: 1) as a dust, 2) as a solution in an organic solvent or a combination of water and one or more organic solvents, or 3) as an emulsion that is prepared by dissolving the product in an organic solvent, then dispersing the solution in water. All of these approaches have drawbacks. Application of a dust is associated with drift, poses a health hazard, and is inefficient. Solutions and emulsions that require an organic solvent are undesirable, since the solvent serves no other purpose but to act as a carrier for the product. As such, the solvent adds an unnecessary cost to the formulation and is an added health risk. Finally, emulsions are generally unstable and must be prepared at point of use, typically in the hours or minutes before use, and minor changes in the formulation, for example by addition of another biocide, may cause the emulsion to break and separate.
The low water solubility is also a factor at point of use. Generally, for low solubility fungicides, the amount of a fungicide needed to protect against various pests is generally dependent on the number of particles in a unit area. If 100 particles are needed on a leaf, and if the particle diameter is reduced to one third of the former diameter, then the dosage can theoretically be reduced to about 11% of the former dosage, resulting in lower cost, less pesticide residue on harvested crops, and mitigation of environmental impact.
It is known to mill certain organic pesticides. For instance, published U.S. Patent Application No. 2001/0051175 A1 describes milling large classes of fungicides with grinding media of substantially spheroidal shaped particles having an average size of less than 3 mm, and teaches that “suitable media material include [s] ZrO stabilized with magnesia, zirconium silicate, glass, stainless steel, polymeric beads, alumina, and titania, although the nature of the material is not believed to be critical.” We believe these inventors were incorrect in their assumption that the grinding material and size were of little importance.
On the other hand, when a breakthrough is made, the product can be very successful. Copper (on a copper metal basis) is generally used as a biocidal agent (depending on crop, application, and activity) at application rates of 0.25 lb to 7.5 lbs per acre. Another biocide is copper hydroxide, which is a preferred low solubility copper salt, and which has >60% by weight copper and a solubility product constant of about 2×10−20. Several years ago, copper hydroxide used for foliar applications had a particle size of about 1 to 3 microns. Then, a new product, Champ DP®, commercially available from Nufarm Americas, was made available with a median particle size of about 0.2 microns. This product was useful at half the application rate on a variety of crops, and the duration of treatment was not appreciably different than that of the products containing larger particles.
This is not to say that all biocides, even all low solubility fungicides, benefit from smaller size. For example, the ubiquitous elemental sulfur is generally advantageously 3 to 5 microns in diameter when used in foliar applications. While smaller particles can be formed, the actions of the atmosphere, moisture, and sunlight combine to eliminate the efficacy of the sulfur particles in too short a time to be of commercial interest. Additionally, particle size reduction below certain values (which depend on the product characteristics) can in the past only be achieved through expensive and elaborate procedures, and such procedures quickly price the product out of the market.
Chlorothalonil is commercially available as a suspension having an average particle size diameter between about 2 and about 5 microns. It is known to mill chlorothalonil, but no milling process had ever achieved a reduction in the d50 (the volume average diameter) below about 2 microns. Backman et al. found that, within the limits tested, the efficacy of Chlorothalonil tended to increase with decreasing particle size and with increasing milling. Beckman tested standard air milled chlorothalonil with wet-milled chlorothalonil. The particle sizes tested are represented below, where the air milled product is the standard, and the hours of wet milling are provided, where “med. μ” is the median diameter in microns (NOT the d50—the d50 will always be much higher than the median diameter), “<1μ, %” is the percentage of particles with a diameter less than 1 micron, and Def(0.42) is the defoliation of Florunner peanuts treated with the amount in parentheses, e.g., 0.42, in kg chlorothalonil per ha, where defoliation was presumed due top leafspot infestation:
Mill<1μ,DefDefDefDefTypeTimemed. μ%(0)(0.42)(0.84)(1.26)1974 dataAir—3.3 7%—392519Wet3 hr3.8 8%—332415.5Wet9 hr1.7522%—3217.214.1Wet13 hr 1.624%—272315.41975 dataAir—3.3 5%39353427Wet3 hr3.710%39352828Wet>9 hr 1.622%37322929
This data generally show that the efficacy of the treatment generally increased with wet milling over air milling, and that the efficacy increased with milling time for the lowest treatment rate, though the data was not conclusive as the efficacy went down with increased milling time at the two higher treatment rates. See Backman, P. A., Munger, G. D., and Marks, A. F., The Effects of Particle Size and Distribution on Performance of the Fungicide Chlorothalonil, Phytopathology, Vol. 66, pages 1242–1245 (1976).
U.S. Pat. No. 5,360,783, the disclosure of which is incorporated herein by reference, particularly noting the milling method and the dispersants and stabilizers disclosed therein, discloses in Example 2 milling Maneb with 2 mm glass beads. The resulting mean particle diameter of the Maneb was 1.7–1.8 micons. Also in this patent, chlorothalonil (Daconil) was milled in the same manner in Test 5, and the resulting average particle size diameter was 2.3 microns.
U.S. Pat. No. 5,667,795, the disclosure of which is incorporated herein be reference, particularly relating to the adjuvants, describes milling 40% chlorothalonil, 5.6% zinc oxide, 6% PLURONIC P-104 (a poly (oxypropylene) block copolymer with poly (oxyethylene), commercially available from BASF), 0.25% xanthan gum (commercially available from Kelco), 0.25% Antifoam FG-10 (silicon emulsion, commercially available from Dow Corning), 1% HI-SIL 233 (precipitated amorphous silica, commercially available from PPG Ind.), 0.4% PVP K-30 (poly(vinyl pyrrolidone), commercially available from BASF), 3% propylene glycol, 0.1% PROXEL GXL (1,2-benzisothiazolin-3-one, commercially available from ICI); 1.5% EDTA, and balance water in a wet mill or high speed media mill. This patent does not describe the milling media, but states the average particle size of the product was 3 microns.
Curry et al. at International Specialty Products have ground a few biocides with 0.1 cm zirconia at 70% to 80% loading. For instance, U.S. Published Patent Application Nos. 2004/0063847 A1 and 2003/0040569 A1 describe milling metaldehyde with a variety of surfactants and dispersants, milling at 0–5° C., and recycling the material at 19 passes per minute for 10 minutes. Fine suspensions were produced with particle size distributions in which 90% of the particles had a diameter less than 2.5 microns, and in which the mean volume diameter was less than 1.5 microns. A chlorothalonil suspension was described as being milled in the same manner, but data on particle size was not reported. However, commonly-assigned U.S. Published Patent Application No. 2004/0024099 A1 described an example where a composition of chlorothalonil was wet milled under the same conditions described above, i.e., a 70% to 80% loading of 0.1 cm zirconium (sp) beads at 3000 rpm for 10 minutes with 19 recycles per minute. The resulting compositions contained 41% chlorothalonil and a variety of surfactants and dispersants. The milling temperature jacket was 0° C., and the milled material was 15–21° C. The publication claims that 90% of the number of particles had a size below 0.5 microns but that the mean volume diameter (d50) was “less than 3 microns”, meaning half the volume of particles had particle sizes greater than “less than 3 microns.” The art uses the term “less than” to denote the maximum mean diameter in a series of tests, but it is well known in the art that routine changes in parameters such as milling time will not appreciably change the mean volume diameter, as discussed infra. The resulting chlorothalonil material made according to the International Specialty Products process thus has a mean volume diameter d50 of 2 to 3 microns. This is consistent with the other disclosures.
The phenomena of a wide particle size distribution should be clarified. The International Specialty Products inventors described their chlorothalonil composition as having 90% of particles below 0.5 microns, but as having a mean volume diameter in the range of 2–3 microns. This wide particle size distribution is common, and it severely limits the benefits of the low particle size product, e.g., when used in paints, wood preservatives, and foliar applications.
For example, in co-pending and commonly-owned U.S. patent application Ser. No. 10/868,967 filed Jun. 17, 2004, we discussed how particles up to 0.5 microns in diameter were injectable into wood. The mean volume diameter of Champ DP®, a small diameter copper salt product, was 0.2 microns. Therefore, one might expect this material to be readily injectable into wood. However, while 57% by weight of particles of copper hydroxide in a particular lot of Champ DP® was 0.2 microns or smaller, when we tried to inject this material into wood this Champ DP® material plugged the surface of the wood and would not penetrate into the wood matrix. We discovered the reason was that there was a critical fraction of particles having a diameter greater than about 1 micron. This critical fraction of material was believed to bridge pores in the wood, and, once the pores were bridged, substantially all the remaining particles, including those having a diameter less than 0.2 microns, subsequently plated on the wood surface.
Further, extended grinding times using milling media routinely used in the art 1) will not provide a more uniform product, and 2) will not significantly lower the d50. It is known that compounds can be reduced to a particular particle size distribution, where further milling with that media has virtually no effect. For example, we milled the Champ DP® material described above (having a d50 of 0.2 microns, but a d95 over a micron) for two days using 2 mm zirconia beads as the media, and the injectability and particle size distribution of the resultant composition was essentially unchanged. Along those lines, U.S. Published Patent Application No. 2004/0050298 A1, in the unrelated art of formulating pigments, discloses that wet milling in a pearl mill with mixed zirconium oxide balls having a diameter of from 0.1 to 0.3 mm could provide a desired product in 20 to 200 minutes, but that longer milling periods had no significant effect on the properties of the product, and that “as a result, the risk of overmilling can be excluded, with very great advantage for the meeting of specifications, especially if it is ensured that the radial speed of the mill is not too high.”
U.S. Published Patent Application No. 2002/0047058 A1, which relates to preparing certain pharmaceutical formulations, discusses milling the pharmaceuticals with 0.5 mm diameter zirconium (sp) media to obtain pharmaceutical formulations having particle diameters less than 0.5 microns. In addition, U.S. Published Patent Application No. 2004/0051084 A1 describes manufacturing polymer particles comprising recurring thiophene units and polystyrenesulfonic acid by oxidative polymerization of ethylenedioxythiophene in the presence of polystyrenesulfonic acid and subsequent milling with 0.5 mm diameter zirconia. Further, U.S. Published Patent Application No. 2002/0055046 A1 describes milling titanium dioxide with zirconia beads which have a diameter of 0.5 mm (manufactured by Nikkato Co., Ltd), where the resultant mean particle diameter of the titanium dioxide was 2.5 microns. Also, several published applications relate to milling photographic compositions with a 0.5 mm zirconia media.
While it is known to grind certain materials to smaller size, certain biocides are particularly resistant to grinding to less than 1 micron diameter. What is needed in the art is a process whereby a wide variety of biocides can be readily milled to a particle size distribution where d50 is less than 1 micron, preferably less than 0.7 microns.
The lowest d50 obtainable from grinding with a particular media will depend on the properties of material being ground. Several biocides can purportedly be milled to a d50 below about 1 micron, and occasionally below 0.5 micron. These biocides therefore have physical properties that differ from those of chlorothalonil, making them easier to grind than chlorothalonil. For example, it has been reported that milling triphenyltin acetate, 1-methyl-3-(2-fluoro-6-chlorophenyl)-5-(3-methyl-4-bromothien-2-yl)-1H-1,2,4-triazole, Spinosad insecticide, epoxiconazole, chlorpyrifos, and certain other materials to sub-micron size using milling materials that are outside the scope of this invention (see, e.g., U.S. Published Patent Application No. 2001/0051175 A1). However, we believe that using the method of this invention will provide a narrower particle size distribution than the prior art milling methods.
What is needed in the art is a process whereby a wide variety of biocides can be readily milled to a particle size distribution where d90 is less than 1 micron, preferably less than 0.7 microns.
Mentioning a reference in this background section is explicitly not a concession that such reference constitutes prior art under the patent laws of any country in which this application is pending. We found no reference in the published applications which relates to milling a sparingly soluble inorganic biocidal compound, for example copper hydroxide, with 0.5 mm zirconia. We found no reference in the published applications which relates to milling an organic fungicide with 0.5 mm zirconia media. We, in particular, found no reference in the published applications which related to milling chlorothalonil with 0.5 mm zirconia media. It would be an advantage in the art to provide a pesticide formulation of fairly uniformly sized submicron organic pesticide particles. It would be an advantage in the art to provide a method to routinely and predictably: 1) prepare a pesticide formulation of fairly uniformly sized submicron organic pesticide particles; 2) a pesticide formulation of fairly uniformly sized submicron organic pesticide particles with sub-micron sparingly soluble inorganic biocidal particles; and 3) a method of manufacturing the aforesaid formulations that will allow the formulation to have commercial application in the fields of a) foliar applications, b) wood preservative treatments, c) turf applications, and d) non-fouling paints and coatings.